Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing enynes

A Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing 1,n‐enynes to give three different types of compounds is discussed. 1,6‐enynes with a stoichiometric amount of FeX₃ provided cis‐hydrobenzofurans with moderate stereoselectivity, whereas the reaction with TMSX (X = Cl, Br) as the halide source in the presence of Fe catalyst improved the stereoselectivity of halide addition highly. The alkyl vs aryl shows difference that the reaction of 1,6‐enynes bearing an alkylethynyl group gave meta alkenated phenols (2 examples) whereas a similar reaction of 1,6‐enynes with an arylethynyl group delivered only cis‐hydrobenzofurans (12 examples). 1,7‐enynes afforded tricyclic products (4 examples). The different reactivity of 1,6‐ and 1,7‐enynes is probably influenced by the formation of a six‐membered chair‐like intermediate in 1,6‐enynes.     

The Photocyclodimers of 2,3‐Dihydro‐2,2‐dimethyl‐4H‐pyran‐4‐one

On irradiation (350 nm) in benzene solution, dihydropyranone 3 affords predominantly (75%) the cis‐anti‐cis HH‐dimer 4 , but in smaller amounts (12%) also dimer 5 , wherein one of the six‐membered rings is trans‐fused to the (central) cyclobutane ring. The constitution and configuration of 5 was fully elucidated by NMR‐analysis. On contact with SiO₂, 5 isomerizes quantitatively to the cis‐anti‐cis HT‐dimer 7 , the structure of which was established by X‐ray crystal‐structure determination.     

Squaramide‐Catalyzed Asymmetric aza‐Friedel–Crafts/N,O‐Acetalization Domino Reactions Between 2‐Naphthols and Pyrazolinone Ketimines

N‐Boc ketimines derived from pyrazolin‐5‐ones were explored to develop an unprecedented domino aza‐Friedel–Crafts/N,O‐acetalization reaction with 2‐naphthols. The novel method requires a catalyst loading of only 0.5 mol % of a bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra‐substituted stereogenic centers in excellent yields (95–98 %) and stereoselectivity (>99:1 d.r. and 97–98 % ee ). A different reactivity was observed in the case of 1‐naphthols and other electron‐rich phenols, which led to the aza‐Friedel–Crafts adducts in 70–98 % yield and 47–98 % ee .     

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

We report a multi‐component asymmetric Brønsted acid‐catalyzed aza‐Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho‐tert‐butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61–98 %) and mostly >90 % optically active cis‐aziridines. (+)‐Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.     

Irreversible helix rearrangement from Cis‐transoid to Cis‐cisoid in poly(p‐n‐hexyloxyphenylacetylene) induced by heat‐treatment in solid phase

Polymerization of p‐n‐hexyloxyphenylacetylene (pHPA) by using a [Rh(norbornadine)Cl]₂‐triethylamine catalyst was carried out at room temperature to afford stereoregular helical poly(p‐n‐hexyloxyphenylacetylene)s (PpHPAs). When ethanol and n‐hexane were used as polymerization solvents, a bright yellow PpHPAs, poly( Y ) with M_n = 8.5 × 10⁴ and its purple red polymer, poly( R ) with M_n = 5.3 × 10⁴ were obtained in 95% yields and 84% yields, respectively. Diffuse reflective UV–vis spectra of poly( Y ) and poly( R ) in solid phase showed different broad absorption peaks at 445 and 575 nm, respectively. X‐Ray diffraction patterns of poly( Y ) and poly( R ) showed typical columnar structures assignable to cis‐transoid and cis‐cisoid structures, respectively, which were also supported by molecule mechanics calculation. Poly( Y ) was irreversibly transformed to a reddish‐black polymer, poly( Y‐B ), which columnar diameter was nearly the same as that of poly( R ). Further, poly( Y ) showed an exothermic peak in the differential scanning calorimetry trace at 80 °C for 1 h in N₂ gas. Thus, these findings suggest a thermally irreversible rearrangement from an unstable cis‐transoid form, poly( Y ) with a stretched cis‐transoid helix to a stable cis‐cisoid form, poly( R ), with a contracted cis‐cisoid helix in the solid phase to give poly( Y → B ) with the cis‐cisoid form. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and Thermal Properties of Regio‐ and Stereoregular Poly(silylene‐1,4‐phenylenevinylene)s

Polymerization of p‐(dimethylsilyl)phenylacetylene in toluene at 25 and 80°C using RhI(PPh₃)₃ as the catalyst afforded highly regio‐ and stereoregular poly(dimethylsilylene‐1,4‐phenylenevinylene)s (cis‐ 3 a and trans‐ 3 a ) containing 98% cis‐ and 99% trans‐vinylene moieties, respectively. Similarly, poly(butylmethylsilylene‐1,4‐phenylenevinylene)s ( 3 b with 91% cis‐ and 95% trans‐structures) and poly(diisopropylsilylene‐1,4‐phenylenevinylene) with 95% trans‐structure were synthesized. All polymers were soluble in common organic solvents. The trans‐type polymers showed red shifts and hyperchromic effects in the UV‐visible spectrum. The onset temperature of weight loss (T₀) of cis‐ 3 a was much higher than that of trans‐ 3 a .     

Theoretical study of the structures,conformations, and spectroscopic properties of 2‐formylthiophene‐N‐acetylhydrazone and 2‐thiophenecarboxaldehyde‐2‐thienylhydrazone

2‐Formylthiophene‐N‐acetylhydrazone (Hait) and 2‐thiophenecarboxaldehyde‐2‐thienylhydrazone (Htit) in the cis and trans conformations were investigated in the gas‐phase by density functional method using B3LYP as the functional set and 6‐311++G(d,p) as the basis set. The cis and trans structures were fully optimized in the C₁ and C_s symmetries. Transition states were also modeled for the cis–trans isomerization of the title compounds and the barriers to internal rotation were calculated. This work reports the structural, energetics, and spectroscopic parameters of all the optimized geometries. Some of the structural parameters are in good agreement with experimental literature data. The computed parameters for these compounds are also in good agreement with a related molecule, namely, acetohydrazide. For both Hait and Htit, the trans conformers are more stable than the cis conformers and the energy barriers are larger compared with the energy differences between the cis and trans conformers. This accounts for Hait and Htit existing mostly in the trans conformation. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:144–150, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20526     

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide is described. In the reaction with allyl bromide, either a Pd(dba)₂? CuI combination (dba, dibenzylideneacetone) in DMF or copper(I) iodide in DMSO–THF readily catalyzes or mediates the coupling reaction of (Z)‐silyl(stannyl)ethenes at room temperature, producing novel vinylsilanes bearing an allyl group β to silicon with cis ‐disposition in good yields. Allyl chlorides as halides can be used in the CuI‐mediated reaction. CuI alone much more effectively mediates the cross‐coupling reaction with propargyl bromide in DMSO–THF at room temperature compared with a Pd(dba)₂? CuI combination catalysis in DMF, providing novel stereodefined vinylsilanes bearing an allenyl group β to silicon with cis ‐disposition in good yields. Copyright © 2008 John Wiley & Sons, Ltd.     

A New Benzotriazole‐Mediated Stereoflexible Gateway to Hetero‐2,5‐diketopiperazines

Open chain Cbz‐L ‐aa¹‐L ‐Pro‐Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans‐ or cis‐fused 2,5‐diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans‐DKPs (69–75 %). Complementarily, tandem deprotection/cyclization led to the cis‐DKPs (65–72 %). A representative set of proline‐containing cis‐ and trans‐DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results.     

Controlled stereochemistry of polyamides derived from cis/trans‐1,4‐cyclohexanedicarboxylic acid

A series of copolyamides 12.y was synthesized either with y = 6, or 1,4‐cyclohexanedicarboxylic acid (1,4‐CHDA) residue, or a mixture of both. The influence of the synthetic route of 1,4‐CHDA containing polyamides on the obtained cis–trans ratio of the incorporated 1,4‐CHDA was investigated. The use of acid chlorides provided a synthetic route with full control of the cis–trans ratio of the 1,4‐CHDA residue during synthesis, whereas synthesis at elevated pressure and temperature caused isomerization. The content and cis–trans ratio of 1,4‐CHDA in the copolyamides were determined by solution ¹³C NMR spectroscopy. Increasing the degree of partial substitution of the adipic acid by 1,4‐CHDA resulted in an increase in T_m, even for low molar precentages of 1,4‐CHDA. This phenomenon points to isomorphous crystallization of both the 12.6 and 12.CHDA repeating units. The mps of the synthesized polyamides were independent of the initial cis–trans ratio of 1,4‐CHDA, provided that the samples were annealed at 300 °C before DSC analysis. The polyamides exhibited a different melting pattern depending on the 1,4‐CHDA content. At a low a 1,4‐CHDA content a net exothermic recrystallization occurred during melting, whereas at higher contents of 1,4‐CHDA this recrystallization occurs to a lesser extent, and two separate melting areas are observed. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 833–840, 2001     

Complexation of 4‐dimethylaminoazobenzene with various kinds of cyclodextrins: Effects of cyclodextrins on the thermal cis‐to‐trans isomerization

On the basis of the change in electronic and induced circular dichroism spectra for complex formation, the complexation of 4‐dimethylaminoazobenzene (DAAB) with four kinds of cyclodextrins (α‐ and β‐cyclodextrin (CD), heptakis(2,6‐di‐O‐methyl)‐β‐cyclodextrin, and heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin) was studied in methanol–water and dimethyl sulfoxide–water mixtures. It was found that the trans and cis isomers of DAAB form two different types of complex (inclusion and lid type) with CDs, depending on the kinds of CDs and solvents. Further, we have examined the effect of CDs on the thermal cis‐to‐trans isomerization of DAAB. The accelerated or decelerated effect on the thermal isomerization was observed upon adding CDs. The effects of CDs on the thermal isomerization are discussed in connection with the complexation of the cis‐isomer of DAAB with CDs. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 481–487, 2002     

Synthesis and properties of blue light‐emitting,silicon‐containing,regio‐ and stereoregular conjugated polymers

This article concerns the hydrosilylation polyaddition of 1,4‐bis(dimethylsilyl)benzene ( 1 ) with 4,4′‐diethynylbiphenyl, 2,7‐diethynylfluorene ( 2b ), and 2,6‐diethynylnaphthalene with RhI(PPh₃)₃ catalyst. Trans‐rich polymers with weight‐average molecular weights (M_w's) ranging from 19,000 to 25,000 were obtained by polyaddition in o‐Cl₂C₆H₄ at 150–180 °C, whereas cis‐rich polymers with M_w's from 4300 to 34,000 were obtained in toluene at 0 °C–r.t. These polymers emitted blue light in 4–81% quantum yields. The cis polymers isomerized into trans polymers upon UV irradiation, whereas the trans polymers did not. The device having a layer of polymer trans‐ 3b obtained from 1 and 2b demonstrated electroluminescence without any dopant. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2774–2783, 2004     

Exceptionally E‐ and β‐Selective NHC–Cu‐Catalyzed Proto‐Silyl Additions to Terminal Alkynes and Site‐ and Enantioselective Proto‐Boryl Additions to the Resulting Vinylsilanes: Synthesis of Enantiomerically Enriched Vicinal and Geminal Borosilanes

An exceptionally site‐ and E‐selective catalytic method for preparation of Si‐containing alkenes through protosilylation of terminal alkynes is presented. Furthermore, the vinylsilanes obtained are used as substrates to generate vicinal or geminal borosilanes by another catalytic process; such products are derived from enantioselective protoborations of the Si‐substituted alkenes. All transformations are catalyzed by N‐heterocyclic carbene (NHC) copper complexes. Specifically, a commercially available imidazolinium salt, cheap CuCl (1.0 mol %) and Me₂PhSi–B(pin), readily and inexpensively prepared in one vessel, are used to convert terminal alkynes to (E)‐β‐vinylsilanes efficiently (79–98 % yield) and in >98 % E and >98 % β‐selectivity. Vinylsilanes are converted to borosilanes with 5.0 mol % of a chiral NHC–Cu complex in 33–94 % yield and up to 98.5:1.5 enantiomeric ratio (e.r.). Alkyl‐substituted substrates afford vicinal borosilanes exclusively; aryl‐ and heteroaryl‐substituted alkenes deliver the geminal isomers preferentially. Different classes of chiral NHCs give rise to high enantioselectivities in the two sets of transformations: C₁‐symmetric monodentate Cu complexes are most suitable for reactions of alkyl‐containing vinylsilanes and bidentate sulfonate‐bridged variants furnish the highest e.r. for substrates with an aryl substituent. Working models that account for the observed trends in selectivity are provided. Utility is demonstrated through application towards a formal enantioselective total synthesis of naturally occurring antibacterial agent bruguierol A.     

Poly[1‐(trimethylgermyl)‐1‐propyne] and poly[1‐(trimethylsilyl)‐1‐propyne] with various geometries: Their synthesis and properties

The polymerization of 1,2‐disubstituted acetylenes [1‐(trimethylgermyl)‐1‐propyne and 1‐(trimethylsilyl)‐1‐propyne] initiated by Nb‐ and Ta‐based catalytic systems was studied within a wide temperature range (?10 to +80 °C) with solvents (cyclohexane, CCl₄, toluene, anisol, and n‐chlorobutane) with variable dielectric constants (2.023–7.390). Conditions ensuring the synthesis of poly[1‐(trimethylsilyl)‐1‐propyne] (PTMSP) containing 20–80% cis units and poly[1‐(trimethylgermyl)‐1‐propyne] (PTMGP) containing 3–65% cis units were determined. The PTMSP and PTMGP samples were amorphous, exhibited a two‐phase structure characterized by the presence of less ordered regions and regions with an enhanced level of ordering, and differed in solubility. A correlation was found between the cis/trans ratio and the morphology, the geometrical density of PTMSP and PTMGP films, and the gas permeability of the polymers. The gas permeability and solubility behavior of PTMSP and PTMGP were examined in terms of the molecular characteristics of the polymer samples (the thermodynamic Kuhn segment and the Kerr electrooptic effect). It was demonstrated that the gas permeability, as well as the solubility of the polymers, was defined by their supramolecular ordering, which depended on the lengths of continuous sequences composed of units of analogous microstructures and on the flexibility of macrochains. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2133–2155, 2003     

Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C₁‐ and C₂‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.     

N‐substituted bis(tetrazol‐5‐yl)diazenes: Synthesis,spectra, X‐ray molecular and crystal structures,and quantum‐chemical DFT calculations

N‐Substituted bis(tetrazol‐5‐yl)diazenes (substituents are 1‐CH₃ ( 3a ), 1‐Ph ( 3b ), 2‐CH₃ ( 3c ), and 2‐^tBu ( 3d )) were synthesized by oxidative coupling of corresponding 5‐aminotetrazoles. All compounds were characterized with ¹H and ¹³C NMR, IR‐ and UV‐spectroscopy, and thermal analysis. Crystal and molecular structures of bis(1‐phenyltetra‐ zol‐5‐yl)diazene ( 3b ) and bis(2‐tert‐butyltetrazol‐5‐yl)diazene ( 3d ) were determined by single crystal X‐ray diffraction. Molecules of these compounds are trans‐isomers in solid. According to X‐Ray data, 3b molecule is S‐trans‐S‐trans conformer, however 3d is S‐cis‐S‐cis one. Quantum‐chemical investigation of geometry and relative stability of cis‐ and trans‐isomers and stable conformations of compounds 3a–d was carried out. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:24–35, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20574     

Total Synthesis of (−)‐Platensimycin by Advancing Oxocarbenium‐ and Iminium‐Mediated Catalytic Methods

(?)‐Platensimycin is a potent inhibitor of fatty acid synthase that holds promise in the treatment of metabolic disorders (e.g., diabetes and “fatty liver”) and pathogenic infections (e.g., those caused by drug‐resistant bacteria). Herein, we describe its total synthesis through a four‐step preparation of the aromatic amine fragment and an improved stereocontrolled assembly of the ketolide fragment, (?)‐platensic acid. Key synthetic advances include 1) a modified Lieben haloform reaction to directly convert an aryl methyl ketone into its methyl ester within 30 seconds, 2) an experimentally improved dialkylation protocol to form platensic acid, 3) a sterically controlled chemo‐ and diastereoselective organocatalytic conjugate reduction of a spiro‐cyclized cyclohexadienone by using the trifluoroacetic acid salt of α‐amino di‐tert‐butyl malonate, 4) a tetrabutylammonium fluoride promoted spiro‐alkylative para dearomatization of a free phenol to assemble the cagelike ketolide core with the moderate leaving‐group ability of an early tosylate intermediate, and 5) a bismuth(III)‐catalyzed Friedel–Crafts cyclization of a free lactol, with LiClO₄ as an additive to liberate a more active oxocarbenium perchlorate species and suppress the Lewis basicity of the sulfonyloxy group. The longest linear sequence is 21 steps with an overall yield of 3.8 % from commercially available eugenol.     

Asymmetric Synthesis of (R)‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases

Stereoselective methods for the synthesis of tetrahydro‐ß‐carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C?C coupling through a Pictet–Spengler reaction of tryptamine and secologanin to exclusively form the (S)‐configured tetrahydro‐ß‐carboline (S)‐strictosidine. Investigating the biocatalytic Pictet–Spengler reaction of tryptamine with small‐molecular‐weight aliphatic aldehydes revealed that the strictosidine synthases give unexpectedly access to the (R)‐configured product. Developing an efficient expression method for the enzyme allowed the preparative transformation of various aldehydes, giving the products with up to >98 % ee. With this tool in hand, a chemoenzymatic two‐step synthesis of (R)‐harmicine was achieved, giving (R)‐harmicine in 67 % overall yield in optically pure form.     

1,3‐dipolar cycloaddition reactions of 2‐substituted azomethine N‐oxides with N‐benzyl maleimides leading to the synthesis of stereoisomers

The azomethine N‐oxides ( 1 ) on reacting with N‐benzylmaleimide ( 2 ) provide a mixture of stereoisomers 2,3‐diphenyl‐5‐benzyl‐4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6–dione derivatives ( 3 ) in good yields. These isomers have been assigned cis and trans configurations ( 3‐A and 3‐B ) with respect to proton C₃‐H on the azomethinic carbon on the basis of their PMR and H‐NMR COSY data. The ratio between cis and trans isomers has been found to be dependent on substituents present at ortho position of C‐phenyl aldehydic moiety. The salient feature of these 1,3‐dipolar cycloaddition reactions lies in that the benzylic protons on N‐benzyl moiety suffer gem coupling, indicating magnetic nonequivalence. J. Heterocyclic Chem.,, (2012).     

Synthesis and Characterization of Enantiomerically Pure cis‐ and trans‐3‐Fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐Oxides as γ‐Homoacetylcholine Mimetics and Inhibitors of Acetylcholinesterase

The title compounds, the P(3)‐axially and P(3)‐equatorially substituted cis‐ and trans‐configured 8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐oxides (=8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphabicyclo[4.4.0]decane 3‐oxides=2‐fluorohexahydro‐6‐(phenylmethyl)‐4H‐1,3,2‐dioxaphosphorino[5,4‐c]pyridine 2‐oxides) were prepared (ee>98%) and fully characterized (Schemes 2 and 3). The absolute configurations were established from that of their precursors, the enantiomerically pure cis‐ and trans‐1‐benzyl‐4‐hydroxypiperidine‐3‐methanols which were unambiguously assigned. Being configuratively fixed and conformationally constrained phosphorus analogues of acetyl γ‐homocholine (=3‐(acetyloxy)‐N,N,N‐trimethylpropan‐1‐aminium), they are suitable probes for the investigation of molecular interactions with acetylcholinesterase. As determined by kinetic methods, all of the compounds are weak inhibitors of the enzyme.